Ganciclovir to Prevent Reactivation of Cytomegalovirus in Patients With Acute Respiratory Failure and Sepsis

NCT ID: NCT04706507

Last Updated: 2025-12-12

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE3
• Total Enrollment: 205 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-06-29
• Study Completion Date: 2025-04-08

Brief Summary

This is a phase 3 study designed to evaluate whether the administration of ganciclovir increases ventilator-free days in immunocompetent patients with sepsis associated acute respiratory failure. Our hypothesis is that IV ganciclovir administered early in critical illness will effectively suppress CMV reactivation in CMV seropositive adults with sepsis-associated acute respiratory failure thereby leading to improved clinical outcomes

Conditions

Acute Respiratory Failure

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

IV Ganciclovir

5mg/kg IV twice daily for 5 days, then followed by IV ganciclovir once daily until hospital discharge

Group Type: EXPERIMENTAL

IV Ganciclovir

Intervention Type: DRUG

For first 5 days, dosing of intravenous ganciclovir is 10 mg/kg daily, given as 5 mg/kg every 12 hours (adjusted for renal function). After first 5 days (up to 28 days) IV ganciclovir 5 mg/kg QD ( adjusted for renal function). A minimum interval of 6 hours is required between the first and second dose.

Placebo

normal saline IV twice daily for 5 days, then followed by IV normal saline once daily until hospital discharge

Group Type: PLACEBO_COMPARATOR

Normal saline

Intervention Type: DRUG

For first 5 days, dosing of intravenous saline is 10 mg/kg daily, given as 5 mg/kg every 12 hours (adjusted for renal function). After first 5 days (up to 28 days) IV saline 5 mg/kg QD ( adjusted for renal function). A minimum interval of 6 hours is required between the first and second dose.

Interventions

IV Ganciclovir

For first 5 days, dosing of intravenous ganciclovir is 10 mg/kg daily, given as 5 mg/kg every 12 hours (adjusted for renal function). After first 5 days (up to 28 days) IV ganciclovir 5 mg/kg QD ( adjusted for renal function). A minimum interval of 6 hours is required between the first and second dose.

Intervention Type: DRUG

Normal saline

For first 5 days, dosing of intravenous saline is 10 mg/kg daily, given as 5 mg/kg every 12 hours (adjusted for renal function). After first 5 days (up to 28 days) IV saline 5 mg/kg QD ( adjusted for renal function). A minimum interval of 6 hours is required between the first and second dose.

Intervention Type: DRUG

Other Intervention Names

Cytovene

Eligibility Criteria

Inclusion Criteria

• Subject/next of kin informed consent
• Age > 18 years
• CMV IgG seropositive by lateral flow assay (LFA) or standard serologic methods
• Receiving care in an ICU
• Acute respiratory failure as defined in Section 4.1.1.
• Expected to require respiratory support for at least 2 more days after randomization
• Infection confirmed or suspected by the treating clinician and felt to be the source of acute respiratory failure (Respiratory failure associated with infection confers at least 2 SOFA points above assumed baseline SOFA score of 0, thereby meeting Sepsis-3 definition).

Exclusion Criteria

• Known or suspected immunosuppression, including:

• HIV+ (i.e. prior positive test or clinical signs of suspicion of HIV/AIDS; a negative HIV test is not required for enrollment)
• stem cell transplantation:

• within 6 months after autologous transplantation or
• within 1 years after allogeneic transplantation (regardless of immunosuppression)
• greater than 1 year of allogeneic transplantation if still taking systemic immunosuppression or prophylactic antibiotics (e.g. for chronic graft versus host disease) Note: if details of stem cell transplantation are unknown, patients who do not take systemic immunosuppression and do not take anti-infective prophylaxis are acceptable for enrollment and randomization.
• solid organ transplantation with receipt of systemic immunosuppression (any time)
• cytotoxic anti-cancer chemotherapy within the past three months (Note: next-of-kin estimate is acceptable)
• congenital immunodeficiency requiring antimicrobial prophylaxis (e.g. TMP-SMX, dapsone, antifungal drugs, intravenous immunoglobulin)
• receipt of one or more of the following in the indicated time period (see Appendix C):

• within 6 months: alemtuzumab, antithymocyte/antilymphocyte antibodies, or other immunosuppressive drugs associated with CMV reactivation Note: if no information on these agents is available in the history and no direct or indirect evidence exists from the history that any condition exists that requires treatment with these agents (based on the investigator's assessment), the subject may be enrolled. For all drug information, next-of-kin estimates are acceptable. See Appendix C for commonly prescribed immunosuppressive agents. Information on the use of biologics with moderate immunosuppressive effect but no known effect on CMV are permitted and will be recorded in the CRFs.
• Expected to survive < 72 hours (in the opinion of the investigator)
• Has been hospitalized for > 120 hours (subjects who are transferred from a chronic care ward, such as a rehabilitation unit, with an acute event are acceptable).
• Pregnant or breastfeeding (either currently or expected within one month). Note: for women of childbearing age (18-60 years, unless documentation of surgical sterilization [hysterectomy, tubal ligation, oophorectomy]), if a pregnancy test has not been done as part of initial ICU admission work-up, it will be ordered stat and documented to be negative before randomization. Both urine and blood tests are acceptable.
• Absolute neutrophil count < 1,000/mm3 (if no ANC value is available, the WBC must be > 2500/mm3)
• Use of anti-CMV drugs (cidofovir, letermovir, foscarnet, valganciclovir, ganciclovir) within seven (7) days of patient randomization.
• Currently enrolled in an interventional trial of an investigational therapeutic agent known or suspected to have anti-CMV activity or to be associated with significant known hematologic toxicity (prior approval required).
• At baseline patients who have both a tracheostomy, and have been on continuous 24-hour chronic mechanical ventilation.
• Patients with Child Class C Cirrhosis.
• Patients with severe (requiring home oxygen) pre-existing interstitial lung disease.
• Allergy to ganciclovir
• Incarcerated

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 85 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Heart, Lung, and Blood Institute (NHLBI)

NIH

Sponsor Role: collaborator

Fred Hutchinson Cancer Center

OTHER

Sponsor Role: lead

Responsible Party

Michael Boeckh

Professor, Vaccine and Infectious Disease Division, Fred Hutch

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Michael Boeckh, MD

Role: PRINCIPAL_INVESTIGATOR

Fred Hutchinson Cancer Center

Locations

University of Colorado Denver

Denver, Colorado, United States

Johns Hopkins University

Baltimore, Maryland, United States

Brigham & Women's Hospital

Boston, Massachusetts, United States

University of Michigan

Ann Arbor, Michigan, United States

Henry Ford Hospital

Detroit, Michigan, United States

Washington University

St Louis, Missouri, United States

Montefioure Medical Center

The Bronx, New York, United States

Duke University

Durham, North Carolina, United States

Wakeforest University, School of Medicine

Winston-Salem, North Carolina, United States

University of Cincinnati

Cincinnati, Ohio, United States

The Cleveland Clinic Foundation

Cleveland, Ohio, United States

Ohio State University Medical Center

Columbus, Ohio, United States

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, United States

Medical College of South Carolina

Charleston, South Carolina, United States

Vanderbilt University

Nashville, Tennessee, United States

Intermountain Medical Center

Murray, Utah, United States

University of Vermont College of Medicine

Burlington, Vermont, United States

Harborview Medical Center

Seattle, Washington, United States

University of Washington Medical Center

Seattle, Washington, United States

University of Wisconsin School of Medicine & Public Health

Madison, Wisconsin, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan: Protocol

View Document

Document Type: Statistical Analysis Plan: Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

1UG3HL147011-01A1

Identifier Type: NIH

Identifier Source: secondary_id

View Link

10547

Identifier Type: OTHER

Identifier Source: secondary_id

RG1121219

Identifier Type: -

Identifier Source: org_study_id